Ganglioside GM1-associated diseases or infections are prevalent world-wide, and hundreds of millions of people are infected, or diagnosed, with ganglioside GM1-associated diseases each year. Exemplary diseases or disorders involving GM1 include, but are not limited to Guillain-Barré Syndrome (GBS), lupus, cholera, and enterotoxigenic Escherichia coli (ETEC) infection. Unfortunately, existing treatments for disorders involving GM1 are limited and often have undesirable side-effects.
For example, conventional treatment strategies for GBS rely heavily on the removal of pathogenic anti-glycolipid antibodies (anti-GM1 antibodies) from the blood. In practice, plasmapheresis and intravenous immunoglobulin (IVIG) have been used extensively for treatment (Buchwald et al, Ann Neurol, 51: 673-680 (2002); Kieseier et al., Curr Opin Neurol, 21: 555-562 (2008)). Both strategies, however, are invasive and remove both nonpathogenic and pathogenic antibodies from circulation, can be painful, and with attendant risk of undesirable side effects including severe anaphylactoid reactions.
Existing cholera treatments such as vaccines are expensive and require complex logistics for distribution. Many countries where cholera is endemic cannot afford even the cheapest of the currently existing cholera vaccines. Due to instability of current vaccine formulations, a temperature-controlled system for distribution is required. Such a requirement increases the cost of cholera vaccines.
The current therapy for ETEC is to initiate treatment with agents such as antidiarrheals, rehydration therapy, and combinations thereof. The majority of the treatments involve the non-specific removal of the toxins from the intestinal tract. Only in moderate to severe cases of diarrhea where distressing or incapacitating symptoms are reported is antimicrobial therapy recommended. ETEC is frequently resistant to common antibiotics such as trimethoprim-sulfamethoxazole and ampicillin. Antibiotics are not usually effective at reducing clinical symptoms of the disease and problems associated with antibiotic resistance can occur. Prophylactic use of antibiotics is not recommended.
Therefore, it is an object of the invention to provide methods and compositions for treating GM1-associated diseases, including cholera, ETEC and GBS.
It is another object of the invention to provide methods and compositions for blocking, inhibiting, or reducing binding of GM1.